Pharmaceutical products are significant portion of the national economy, and the process used by pharmaceutical companies to produce these products are regulated by the Food and Drug Administration (FDA). The Division of Manufacturing and Product Quality requires Good Manufacturing Practice for the production of human use pharmaceuticals. The FDA regulates the production of pharmaceuticals to ensure that the methods utilized produce a pharmaceutical products are of high quality and provides Certificates of Pharmaceutical Products to firms that legally market drug products.
The production of medicines requires the utilization of mechanical methods for manipulation of solid and fluid chemical compounds and mixtures. More specifically the transfer of chemical and biological solutions and mixtures will require the use of equipment that is able to be thoroughly cleaned and sanitized preventing contamination of in subsequent use. Improperly sanitizing equipment can result in contamination of the products produced in subsequent batches adding considerable cost. Steam sterilization is currently a preferred method of sanitizing equipment used in pharmaceutical manufacturing. Valves are of significant importance as equipment used in pharmaceutical manufacturing because they are often used to control the flow and transfer of chemicals including biologics and biological organisms.
Because in ordinary valves closing the valve causes the valve's stem to protrude into the flow area and opening the valve causes the stem to retract into the stem's housing area, often chemicals that are in the flow area may get trapped between the middle of the stem and the stem's housing area. The trapped chemicals are often difficult to remove during a sanitizing process allowing the trapped chemicals to be reintroduced into the flow area when the valve is subsequently used.
To overcome sanitation problems in using ordinary valves for the production of pharmaceutical and biological products, sanitary diaphragm valves have been developed. In a sanitary diaphragm valves a diaphragm is introduced between the stem and the flow area. The diaphragm is a flexible material that has a chemical contact side and a stem contact side. During rotation of the handle, the stem contacts the diaphragm pushing the diaphragm's chemical contact side into the flow area forming a seal with the surrounding flow housing area obstructing the flow of solutions. Sanitary diaphragm valves are widely used in the pharmaceutical and biotechnology industries for the processing of therapeutic and biological medicines. These valves have the feature that the diaphragm's chemical contact surface can be steam sterilized. This is typically done in advance of fluid processing in order to reduce the chance that unwanted chemicals are introduced into the drug product.
One major problems of using diaphragms in current valves is that the diaphragm can warp and/or become irregular and may not seal properly when the operator manually closes the valve because the diaphragms are exposed to the extreme conditions of the steam sterilization procedure multiple times and because over exertion of pressure from the stem due to over rotating the handle. Because current valve diaphragm designs utilizes a stem with a fixed operation range, obtaining a proper closure seal depends on proper placement of the diaphragm to prevent leakage from the valve due to improper sealing.
Pharmaceutical and biotechnology companies recognize the warping and sealing problems of current diaphragm valves for some time and many have instituted preventative maintenance programs that require regular replacement of diaphragms. Unfortunately, these measures have not provided to be a satisfactory solution because it is not easy to predict when diaphragm warping will occur and typically the problem is detected too late—generally after a biological contamination that resulted from a breach to the sterile barrier. In addition, the success of diaphragm replacement can vary from operator to operator and therefore may require labor intensive leak testing and re-replacement in order to assure no leaks are present for a even new diaphragm.